The objectives of this research project are twofold: (a) To understand the folding, mechanism, and evolutionary relationships between redox metalloproteins such as cytochromes c and investigate the evolutionary development of the respiratory and photosynthetic electron transport chains of which they are a part; and (b) To discover the molecular basis for genetic control in the lactose system by an x-ray and chemical examination of the repressor-operator complex. We have solved the structures of ferri- and ferrocytochrome c from tuna to 2.0 A resolution, and are measuring and refining coordinates. We have also determined the x-ray structure (2.5 A) and amino acid sequence of c550 from M. denitrificans, and are at the 4.0 A stage with c551 from P. aerugiosa. We plan to extend this study to cytochromes of sulfate-respiring bacteria. We have begun purifying lactose repressor protein from E. coli in collaboration with Arthur Riggs of City of Hope. Synthetic operator DNA (21 base pairs) is being prepared by Dr. Keiichi Itakura, who will join the Caltech group early in 1975. The goal is an x-ray analysis of the repressor-operator complex. Chemical studies and operator base modification studies, are also planned.